Propofol-Induced Metabolic, Apoptotic, and Wnt-Frizzled-Related Transcript Changes in MIA PaCa-2 Cells: In Vitro and Bioinformatic Analyses.

Pancreatic ductal adenocarcinoma (PDAC) remains a highly lethal malignancy, and there is continuing interest in whether agents used during the perioperative period influence tumour-cell biology. Propofol has been associated with antiproliferative and pro-apoptotic effects in experimental cancer models; however, its relationship with Wnt-Frizzled-related transcriptional responses in pancreatic cancer cells remains incompletely characterised. MIA PaCa-2 cells were exposed to propofol for 24 h. Cellular metabolic activity was assessed using the MTT assay over a concentration range of 0-20 µM, and apoptosis was evaluated via Annexin V-FITC/7-AAD flow cytometry at the MTT-derived IC50 concentration of 7.6 µM. Transcript abundance of 18 pathway-associated genes was analysed via RT-qPCR following exposure to 7.6 µM propofol. MTT, flow-cytometry, and RT-qPCR assays were each performed in three independent biological experiments (n = 3). RT-qPCR results were evaluated after Benjamini-Hochberg false discovery rate correction across the 18-transcript panel. Complementary bioinformatic analyses were performed solely to provide exploratory biological and clinical context for the experimentally prioritised transcripts. Propofol produced a concentration-dependent reduction in normalised MTT metabolic activity, with an MTT-derived IC50 of 7.6 µM. At this concentration, total apoptosis increased from 0.67 ± 0.11% in vehicle-treated cells to 17.04 ± 2.40% following propofol exposure (p < 0.001), whereas necrosis remained minimal. The viable-cell fraction decreased from 99.30 ± 1.057% to 82.80 ± 0.841% (p < 0.05). The difference between the MTT-derived IC50 and the Annexin V/7-AAD viable-cell fraction indicates that the MTT-derived IC50 reflects reduced metabolic activity rather than 50% cell lethality. RT-qPCR showed decreased WNT5B, FZD5, and WNT11 transcript abundance and increased GSK3B transcript abundance. All four remained significant after Benjamini-Hochberg correction (WNT5B, q = 0.001; FZD5, q = 0.001; WNT11, q = 0.027; GSK3B, q = 0.041). Exploratory bioinformatic analyses showed heterogeneous gene-specific expression, survival, genomic, immune-infiltration, and dependency patterns and were not interpreted as evidence of a propofol-mediated mechanism in patients. Under the tested in vitro conditions, propofol reduced MTT-derived metabolic activity, increased apoptosis, and was associated with selective Wnt-Frizzled-related transcript changes in MIA PaCa-2 cells. These transcript-level observations do not establish direct functional modulation of Wnt-Frizzled signalling or demonstrate that this pathway mediates the observed apoptotic response. The bioinformatic findings provide exploratory contextual information only. Further validation in additional PDAC and non-malignant pancreatic cell models, together with protein-, phosphorylation-, and pathway-level functional studies, is required.